Prader-Willi syndrome (PWS) is a disorder caused by the inheritance of a paternally derived deletion of the long arm of chromosome 15 and is characterized by abnormalities in physical and mental development.

Detectable by high-resolution chromosome analysis or FISH with specific probes

Paternally derived chromosome has been deleted (maternal genes are inactive due to genomic imprinting)

Maternal disomy- receiving 2 copies of the maternal 15th chromosome and no paternal copies of the 15th chromosome (~24% of cases)

Clinical differences exist between deletion patients and those with maternal disomy. Maternal disomy patients are less likely to have typical facial characteristics, slightly higher IQs and milder behavior problems.*

A defect in the imprinting process occurs due to problems associated with the imprinting center, such as a mutation or deletion resulting in the biparental inheritance and a maternal-only pattern (1% of cases)

In all cases where there has been a recurrence of Prader-Willi syndrome, there has been an imprinting mutation.

High resolution chromosome analysis alone is insufficient due to false positives and false negatives

Uniparental disomy can be identified using microsatellite repeat sequences from chromosome 15 in the patients and the parents; if none of the variants of these repeats that are present in the father are seen in the child, then all the genetic information from chromosome 15 has been maternally derived.

Intervention and management of PWS can significantly impact the health, functional abilities, and life of patients.

Infantile FTT-

Special feeding techniques are required because breast feeding is usually inhibited by the hypotonia

Short Stature-

Growth hormone has been shown to increase height and muscle tone

Good results have been shown for adolescents.

Development and behavior-

Closely monitor development and behavior in infancy and toddler-hood.

Developmental assessments should be conducted on patients and they should have early intervention services as soon as possible.

Educational intervention should occur throughout school years. Most children require special education classes, speech therapy, and physical/occupational therapies.

It is important to apply specific and consistent limits at home and school. Most individuals require consistency in daily routines and should be prepared in advance for changes in routine or activities.

Those with severe behavioral problems may respond to psychotherapy. Medication for treatment of psychiatric problems is often needed.

Obesity-

Avoidance of obesity is extremely important, yet very difficult to achieve.

Close monitoring of weight percentiles and height to weight ratio is critical throughout life

Those who are extremely obese should have an assessment of glycosylated hemoglobin levels

Decrease caloric intake, to1000-1200 Kcal/day or less.

Vitamins and calcium should be taken everyday (100% of daily recommended)

Keeping food under lock and only keeping healthy low calorie food in the house is critical

Involve teachers and employers of individuals with PWS in food monitoring

Regular exercise is extremely important; a program should be initiated as early as possible.

Hypotonia-

Physical therapy is appropriate

Evaluation of hypothyroidism if hypotonia is persistant

Hypogonadism (endocrine)-

Administration of hCG may stimulate testicular descent

Administration of testosterone in males or estrogen in females to improve secondary sex characteristics

Ophthalmologic-

Exams to monitor strabismus, myopia and hyperopia

Dental-

Emphasis placed on good dental hygiene

Products that increase saliva flow can be used as necessary

Musculoskeletal-

Scoliosis should be monitored and treated as in the general population

Calcium and vitamin D levels should be assured

Dermatologic-

Examination of the skin should occur to monitor the presence of sores from skin picking